B cell TLR7 expression drives anti-RNA autoantibody production and exacerbates disease in systemic lupus erythematosus-prone mice.
B cell TLR7 expression drives anti-RNA autoantibody production and exacerbates disease in systemic lupus erythematosus-prone mice.
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DOI：
10.4049/jimmunol.1202195
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发表时间：
2012-12-15
期刊：
影响因子：
--
通讯作者：
Fairhurst AM
中科院分区：
文献类型：
--
作者：
Hwang SH;Lee H;Yamamoto M;Jones LA;Dayalan J;Hopkins R;Zhou XJ;Yarovinsky F;Connolly JE;Curotto de Lafaille MA;Wakeland EK;Fairhurst AM
系统性红斑狼疮（SLE）是一种以产生抗核自身抗体（ANA）为特征的慢性系统性自身免疫性疾病。ANA发展被认为是疾病的初始阶段之一，通常导致全身性炎症，肾脏疾病和死亡。病因是复杂的，但很明显，先天途径可能在疾病进展中发挥重要作用。最近的数据突出了TLR家族的重要作用，特别是TLR 7在人类疾病和鼠模型中。在本文所述的研究中，我们提出了一种低拷贝条件性TLR 7转基因（Tg 7）小鼠品系，其不产生自发性自身免疫。当我们将联合收割机Tg 7与Sle 1狼疮易感基因位点结合时，小鼠会患上严重的疾病。使用CD 19 Cre重组酶系统，我们仅在B细胞内标准化TLR 7的表达。使用这种方法，我们证明了在B细胞隔室中TLR 7的过表达减少了边缘区B细胞隔室，并增加了B和T细胞活化，但不增加T滤泡辅助细胞的发育。此外，这种增强的B细胞TLR 7表达允许针对RNA/蛋白质复合物的抗体的特异性发展，并加剧SLE疾病。
Systemic Lupus Erythematosus (SLE) is a chronic systemic autoimmune disease characterized by the production of anti-nuclear autoantibodies (ANA). ANA development is recognized as one of the initial stages of disease which often results in systemic inflammation, kidney disease and death. The etiology is complex, but it is clear that innate pathways may play an important role in disease progression. Recent data has highlighted an important role for the TLR family, particularly TLR7 in both human disease and murine models. In the studies presented here, we have presented a low copy conditional TLR7 transgenic (Tg7) mouse strain which does not develop spontaneous autoimmunity. When we combine Tg7 with the Sle1 lupus susceptibility locus, the mice develop severe disease. Using the CD19Cre-recombinase system, we normalized expression of TLR7 solely within the B cells. Using this method we demonstrated that overexpression of TLR7 within the B cell compartment reduces the marginal zone B cell compartment and increases B and T cell activation but not T follicular helper cell development. Moreover, this enhanced B-cell TLR7 expression permits the specific development of antibodies to RNA/protein complexes and exacerbates SLE disease.
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影响因子：
4.9
作者：
Kawasaki A;Furukawa H;Kondo Y;Ito S;Hayashi T;Kusaoi M;Matsumoto I;Tohma S;Takasaki Y;Hashimoto H;Sumida T;Tsuchiya N
通讯作者：
Tsuchiya N
影响因子：
4.6
作者：
Kim, J. R.;Mathew, S. O.;Mathew, P. A.
通讯作者：
Mathew, P. A.
影响因子：
5
作者：
Graham, D. S. Cunninghame;Vyse, T. J.;Rioux, J. D.
通讯作者：
Rioux, J. D.
DOI：
10.1007/978-1-60327-019-9_16
发表时间：
2009-01-01
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Birling, Marie-Christine;Gofflot, Francoise;Warot, Xavier
通讯作者：
Warot, Xavier
影响因子：
158.5
作者：
Arbuckle, MR;McClain, MT;Harley, JB
通讯作者：
Harley, JB